The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis

Autores
Gómez, Florencia; Schweitzer, Karen; Curino, Alejandro Carlos; Facchinetti, Maria Marta; Giorgi, Gisela
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
We have previously reported that the overexpression of Heme Oxygenase-1 (HO- 1), an enzyme that catalyzes heme degradation and releases iron, impairs breast cancer (BC) cell survival in human triple-negative (MDA-MB-231) BC cell lines, most likely through ferroptosis induction. In this study, we aimed to evaluate the effect of hemin, a drug commercially available thatmodulates the activity of HO- 1, in the modulation on hormone-dependent and independent BC cell survival and to assess the involvement of HO-1. To this end, we treated the T47D and MDA-MB-231 cell line with hemin (36h). We studied cell viability (crystal violet), iron storage (Prussian blue), ROS levels (DFCA), lipid peroxidation (MDA accumulation) and the expression of the iron importer ZIP14 (immunocytochemistry). We found that hemin treatment decreased T47D and MDA-MB231 cell viability (p<0.01 in both) and increased iron storage (p<0.05 in both), ROS levels (p<0.05 and p<0.001 respectively), MDA accumulation (p<0.01 in both) and ZIP14 expression. The treatment with iron chelator (deferoxamine) reversed the reduction of cell viability induced by hemin in both cell lines (p<0.001 in both). When HO-1 was inhibited with SNPP in MDA-MB231 cells, we detected an increase in the cell viability (p<0.01). Similarly, the overexpression of an enzymatically inactive HO-1 in T47D increased the cell viability (p<0.05). In conclusion, the hemin effect on the BC cells would be independent of the breast tumor subtype. In hormone-dependent and independent BC, the hemin impairs cell viability through the HO-1 induction that produces an increase in free iron accumulation, ROS production and lipid peroxidation, being the enzymatic activity of HO-1 necessary for the hemin effect on cell viability.
Fil: Gómez, Florencia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LVI Reunión Anual de Asociación Argentina de Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
Universidad Nacional del Sur
Materia
HEMIN
BREAST CANCER
HO-1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/278617
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/278617
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” AxisGómez, FlorenciaSchweitzer, KarenCurino, Alejandro CarlosFacchinetti, Maria MartaGiorgi, GiselaHEMINBREAST CANCERHO-1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously reported that the overexpression of Heme Oxygenase-1 (HO- 1), an enzyme that catalyzes heme degradation and releases iron, impairs breast cancer (BC) cell survival in human triple-negative (MDA-MB-231) BC cell lines, most likely through ferroptosis induction. In this study, we aimed to evaluate the effect of hemin, a drug commercially available thatmodulates the activity of HO- 1, in the modulation on hormone-dependent and independent BC cell survival and to assess the involvement of HO-1. To this end, we treated the T47D and MDA-MB-231 cell line with hemin (36h). We studied cell viability (crystal violet), iron storage (Prussian blue), ROS levels (DFCA), lipid peroxidation (MDA accumulation) and the expression of the iron importer ZIP14 (immunocytochemistry). We found that hemin treatment decreased T47D and MDA-MB231 cell viability (p<0.01 in both) and increased iron storage (p<0.05 in both), ROS levels (p<0.05 and p<0.001 respectively), MDA accumulation (p<0.01 in both) and ZIP14 expression. The treatment with iron chelator (deferoxamine) reversed the reduction of cell viability induced by hemin in both cell lines (p<0.001 in both). When HO-1 was inhibited with SNPP in MDA-MB231 cells, we detected an increase in the cell viability (p<0.01). Similarly, the overexpression of an enzymatically inactive HO-1 in T47D increased the cell viability (p<0.05). In conclusion, the hemin effect on the BC cells would be independent of the breast tumor subtype. In hormone-dependent and independent BC, the hemin impairs cell viability through the HO-1 induction that produces an increase in free iron accumulation, ROS production and lipid peroxidation, being the enzymatic activity of HO-1 necessary for the hemin effect on cell viability.Fil: Gómez, Florencia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLVI Reunión Anual de Asociación Argentina de Farmacología ExperimentalBahía BlancaArgentinaAsociación Argentina De Farmacología ExperimentalUniversidad Nacional del SurAsociación Argentina De Farmacología Experimental2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278617The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis; LVI Reunión Anual de Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 55-55978-631-90806-0-5CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-01-14T12:47:58Zoai:ri.conicet.gov.ar:11336/278617instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-01-14 12:47:58.204CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
title The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
spellingShingle The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
Gómez, Florencia
HEMIN
BREAST CANCER
HO-1
title_short The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
title_full The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
title_fullStr The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
title_full_unstemmed The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
title_sort The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis
dc.creator.none.fl_str_mv Gómez, Florencia
Schweitzer, Karen
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author Gómez, Florencia
author_facet Gómez, Florencia
Schweitzer, Karen
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author_role author
author2 Schweitzer, Karen
Curino, Alejandro Carlos
Facchinetti, Maria Marta
Giorgi, Gisela
author2_role author
author
author
author
dc.subject.none.fl_str_mv HEMIN
BREAST CANCER
HO-1
topic HEMIN
BREAST CANCER
HO-1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have previously reported that the overexpression of Heme Oxygenase-1 (HO- 1), an enzyme that catalyzes heme degradation and releases iron, impairs breast cancer (BC) cell survival in human triple-negative (MDA-MB-231) BC cell lines, most likely through ferroptosis induction. In this study, we aimed to evaluate the effect of hemin, a drug commercially available thatmodulates the activity of HO- 1, in the modulation on hormone-dependent and independent BC cell survival and to assess the involvement of HO-1. To this end, we treated the T47D and MDA-MB-231 cell line with hemin (36h). We studied cell viability (crystal violet), iron storage (Prussian blue), ROS levels (DFCA), lipid peroxidation (MDA accumulation) and the expression of the iron importer ZIP14 (immunocytochemistry). We found that hemin treatment decreased T47D and MDA-MB231 cell viability (p<0.01 in both) and increased iron storage (p<0.05 in both), ROS levels (p<0.05 and p<0.001 respectively), MDA accumulation (p<0.01 in both) and ZIP14 expression. The treatment with iron chelator (deferoxamine) reversed the reduction of cell viability induced by hemin in both cell lines (p<0.001 in both). When HO-1 was inhibited with SNPP in MDA-MB231 cells, we detected an increase in the cell viability (p<0.01). Similarly, the overexpression of an enzymatically inactive HO-1 in T47D increased the cell viability (p<0.05). In conclusion, the hemin effect on the BC cells would be independent of the breast tumor subtype. In hormone-dependent and independent BC, the hemin impairs cell viability through the HO-1 induction that produces an increase in free iron accumulation, ROS production and lipid peroxidation, being the enzymatic activity of HO-1 necessary for the hemin effect on cell viability.
Fil: Gómez, Florencia. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Giorgi, Gisela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
LVI Reunión Anual de Asociación Argentina de Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
Universidad Nacional del Sur
description We have previously reported that the overexpression of Heme Oxygenase-1 (HO- 1), an enzyme that catalyzes heme degradation and releases iron, impairs breast cancer (BC) cell survival in human triple-negative (MDA-MB-231) BC cell lines, most likely through ferroptosis induction. In this study, we aimed to evaluate the effect of hemin, a drug commercially available thatmodulates the activity of HO- 1, in the modulation on hormone-dependent and independent BC cell survival and to assess the involvement of HO-1. To this end, we treated the T47D and MDA-MB-231 cell line with hemin (36h). We studied cell viability (crystal violet), iron storage (Prussian blue), ROS levels (DFCA), lipid peroxidation (MDA accumulation) and the expression of the iron importer ZIP14 (immunocytochemistry). We found that hemin treatment decreased T47D and MDA-MB231 cell viability (p<0.01 in both) and increased iron storage (p<0.05 in both), ROS levels (p<0.05 and p<0.001 respectively), MDA accumulation (p<0.01 in both) and ZIP14 expression. The treatment with iron chelator (deferoxamine) reversed the reduction of cell viability induced by hemin in both cell lines (p<0.001 in both). When HO-1 was inhibited with SNPP in MDA-MB231 cells, we detected an increase in the cell viability (p<0.01). Similarly, the overexpression of an enzymatically inactive HO-1 in T47D increased the cell viability (p<0.05). In conclusion, the hemin effect on the BC cells would be independent of the breast tumor subtype. In hormone-dependent and independent BC, the hemin impairs cell viability through the HO-1 induction that produces an increase in free iron accumulation, ROS production and lipid peroxidation, being the enzymatic activity of HO-1 necessary for the hemin effect on cell viability.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/278617
The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis; LVI Reunión Anual de Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 55-55
978-631-90806-0-5
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278617
identifier_str_mv The Hemin Treatment Impairs the Cell Survival of Hormone-Dependent and Hormone-Independent Human Breast Cancer Through the Regulation of “HO-1/Iron” Axis; LVI Reunión Anual de Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 55-55
978-631-90806-0-5
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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